Interakcija inhalacijskih anestetika i citostatika

Abstract

Inhaled anesthetics are often used for inducing or maintaining anesthesia in cancer patients as the length and complexity of the surgical procedure cannot be predicted for it depends on intraoperative surgical and pathohistological findings, and as often as not requires repeated operations for removal or reduction of the primary tumor, regional metastases, recurrence, pathological fractures, or surgery complications. These are easily volatile liquids that enter the body through inhalation, and then, by diffusion through the aleveolocapillary membrane, they are transferred into the blood stream to be transported to all other organs and the central nervous system. Most of the inhaled anesthetics are eliminated from the body through respiration; a portion of them, however, metabolizes in the liver via the cytochrome P450 oxidase family and is excreted via the kidneys, so the issue of their toxicity has always attracted a considerable interest from investigators. Cancer patients receiving cytostatic agents during the perioperative period increase in number every day. Aside from their planned surgery, cancer patients receiving cytostatics also undergo emergency surgery either for their disease complication or for another reason. It is important to understand the pharmacology of cytostatics, their interaction with anesthetics, pharmacokinetics and toxic reactions. Cytostatics and general anesthetics act immunosuppressively and thus compromise the patient’s immune status. In addition, cytostatics depress the myocardium and damage lung function, which can cause serious problems during anesthesia. Each anesthesia as well as each surgery produce stress on the body, and the anesthetics themselves alter the cell immunity so the patients receiving cytostatics during their perioperative period can experience serious general and organ-specific side effects. It would be worth knowing whether any of the most commonly used anesthetics today show an advantage in treating patients withcancer, especially patients receiving chemotherapy, and whether the inhaled anesthetics combined with cytostatics increase, enhance or even suppress the individual effect on various types of cells, above all on tumor cells that can become resistant to therapy for developing the so-called „multidrug resistance“.Inhalacijski anestetici često se primjenjuju za uvod u anesteziju ili za održavanje anestezije kod onkoloških bolesnika zbog toga što se kod uvoda u anesteziju dužina i opseg operacijskog zahvata često ne mogu predvidjeti i ovise o intraoperacijskom kirurškom i patohistološkom nalazu, a nerijetko su potrebne ponavljane operacije zbog uklanjanja ili redukcije primarnog tumora, regionalnih metastaza, recidiva bolesti, udaljenih metastaza, patoloških fraktura ili zbog komplikacija same operacije. To su lako hlapljive tekućine koje u organizam ulaze udisanjem, a zatim difuzijom kroz alveolokapilarnu membranu prelaze u krvotok, krvotokom se dopremaju do svih ostalih organa i do središnjeg živčanog sustava. Veći dio inhaliranih anestetika se eliminira iz organizma respiracijom, me|utim jedan dio metabolizira se u jetri putem obitelji citokrom oksidaza P450 i izlučuje putem bubrega te je pitanje njihove toksičnosti oduvijek izazivalo veliki interes istraživača. Svakodnevno se povećava broj onkoloških bolesnika koji u periperacijskom periodu primaju citostatike. Osim planiranih operacijskih zahvata onkološki bolesnici koji primaju citostatike podvrgavaju se i hitnim operacijskim zahvatima, bilo zbog komplikacija bolesti ili zbog nekog drugog razloga. Važno je razumjeti farmakologiju citostatika, interakciju s anesteticima, farmakokinetiku i toksične reakcije. Citostatici i opći anestetici djeluju imunosupresivno na bolesnika te kompromitiraju njegov imunološki status. Osim toga, citostatici deprimiraju miokard i oštećuju plućnu funkciju, što može izazvati ozbiljne probleme u anesteziji. Svaka anestezija i operacija predstavlja stres za organizam, a sami anestetici mijenjaju staničnu imunost, te bolesnici koji primaju citostatike u perioperacijskom periodu mogu imati ozbiljne opće i organ specifične nuspojave. Bilo bi dobro znati ima li neki od danas najčešće upotrebljavanih anestetika prednost u primjeni kod onkoloških bolesnika, osobito ako ti bolesnici primaju citostatike te da li inhalacijski anestetici i citostatici u kombinaciji povećavaju, potenciraju ili čak suprimiraju pojedinačni učinak na različite vrste stanica, osobito tumorskih stanica koje mogu postati rezistentne na terapiju zbog tzv. „multidrug resistance“

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